Macrophage colony-stimulating factor promotes cell survival through Akt/protein kinase B.
J Biol Chem
; 274(37): 26393-8, 1999 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-10473597
ABSTRACT
The signaling pathways activated by the macrophage colony-stimulating factor (M-CSF) to promote survival of monocyte and macrophage lineage cells are not well established. In an effort to elucidate these pathways, we have used two cell types responsive to M-CSF NIH 3T3 fibroblasts genetically engineered to express human M-CSF receptors (3T3-FMS cells) and human monocytes. M-CSF treatment induced M-CSF receptor tyrosine phosphorylation and recruitment of the p85 subunit of phosphatidylinositol 3-kinase (PI3K) to these receptors. These M-CSF receptor events correlated with activation of the serine/threonine kinase Akt. To clarify that PI3K products activate Akt in response to M-CSF, NIH 3T3 fibroblasts expressing mutant human M-CSF receptors (3T3-FMS(Y809F)) that fail to activate Ras in response to M-CSF also exhibit increased Akt kinase activity in response to M-CSF challenge. Furthermore, Akt appears to be the primary regulator of survival in 3T3-FMS cells, as transfection of genes encoding dominant-negative Akt isoforms into these fibroblasts blocked M-CSF-induced survival. In normal human monocytes, M-CSF increased the levels of tyrosine-phosphorylated proteins and induced Akt activation in a PI3K-dependent manner. The PI3K inhibitor LY294002 blocked M-CSF-mediated monocyte survival, an effect that was partially restored by caspase-9 inhibitors. These data suggest that M-CSF may induce cell survival through Akt-induced suppression of caspase-9 activation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Supervivencia Celular
/
Factor Estimulante de Colonias de Macrófagos
/
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos